Myricetin Inhibit Tumor Growth Via Inhibiting Angiogenesis Research

ObjectiveSince the health environment of human life has been greatly improved,malignant tumors have become a major threat to human health and life quality.Among them,breast cancer is the most common malignant tumor among women in the world,with the second highest new cases and death rate in the world,only after lung cancer.Tumor metastasis is the main cause of failure of clinical treatment and poor quality of life.Tumor vascular have its special structural characteristics and it can provide kinds of nutrients for the growth of tumor cells,which plays an important role in tumor and metastasis.Therefore,inhibiting tumor angiogenesis chould inhibit tumor growth and tumormetastasis.Myricetin is a kind of polyhydroxy flavonols and also Flavonoids ingredients of Traditional Chinese medicine which has the anti-cancer andanti-atherosclerosis function.It also has protective effect of Ischemia reperfusion injury,Myocardial infarction and hypertension disease.It is reported that Myricetin can reduced the secretion levels of the vascular endothelial growth factor(VEGF)in human Ovarian cancer cell.Via breast cancer transplantation tumor model mice,this study was to investigate if Myricetin could anti-tumor and anti-angiogenesis,and revealed the molecule mechanism of action.Methods1.Myricetin effects on tumor-growth and tumor-induced angiogenesis was detected by mice breast cancer model.2.Study the effection on inhibit angiogenesis by Myricetin with chicken embryos villi allantois membrane model(CAM)and the yolk sac membrane model(YSM).3.CCK8 assay were showed the cell proliferation effects by different concentration Myricetin treatment of human umbilical vein endothelial cells(HUVEC)and cancer cells.4.Rat arterial ring assay and HUVEC Transwell assay were detected to explore the effect of Myricetin anti-angiogenesis.5.HUVEC were incubated by VEGF for 10min and then treated with Myricetin for 4h,after that the expression levels of VEGFR2 and p38MAPK were detected by western blotting.Results1.Myricetin has inhibitory effect on tumor growth in mice and tumor angiogenesis.Compared the tumor volume and weight,the experimental results showed that Myricetin inhibits breast tumor growth in mice(P<0.05).In terms of the less CD31 expression in tumor tissues of experiment group,Tumor angiogenesis also be inhibited by Myricetin.(P<0.05).2.chicken embryos villi allantois membrane model(CAM)and the yolk sac membrane model(YSM)found that Myricetin could reduce blood vessel formation.Myricetin with chicken embryos villi allantois membrane model(CAM)and the yolk sac membrane model(YSM)showed that the vascular density of experimental group less than the control group meanwhile the growth rate of experimental group slower than the control group(P<0.05).And the inhibition degree are concentration-dependent.3.CCK8 result showed that Myricetin inhibited breast cancer cells proliferation while had no effect on HUVECCCK8 result showed that Myricetin inhibited mice breast cancer 4T1 cells and human breast cancer 231 cells proliferation(P<0.05),while had no effect on HUVEe(0-100? M).4.Rat arterial ring and Transwell assay showed that Myricetin could effect blood vessel formation.Rat arterial ring showed that the experimental group blood vessels formed relatively less than the control group and it couldn' t see any tubular structure.Transwell assay showed that HUVEC cells number on the experimental group though the Polycarbonate membrane less than the control group(P<0.05).The inhibition degree is correlated to the drug dose.5.VEGFR2 and p38MAPK decreased by treatment of Myricetin on HUVECVEGFR2 and p38MAPK expression of HUVEC decreased with Myricetin treatment after stimulated by VEGF.Conclusion1.Myricetin inhibits tumor-induced angiogenesis and inhibit the growth of breast cancer.2.Myricetin inhibits blood vessel formation.3.Myricetin inhibits breast cancer cells proliferation,but had no influence on endothelial cells proliferation.4.Myricetin inhibits the fuction of blood vessel formation.5.Myricetin inhibits tumor angiogenesis via down-regulate VEGFR2 and P38MAPK.